The specific aim of this pilot project is to test the hypothesis that zinc deficiency enhances the development of experimental oral cancer in rats. It is based on the observation that, in rats, zinc deficiency causes changes in the direction of epithelial dysplasia in regions of oral mucosa and on reports that zinc deficiency enhances the development of esophageal cancer, the epithelium of which has many similarities to regions of oral epithelium. Whereas the evidence for the enhancement of esophageal cancer in rats is quite conclusive, for oral cancer it is inconclusive and needs clarification. The results of the proposed pilot study are to be used as the basis for studies in depth designed to elucidate the role of zinc in the development of oral cancer. As it is in rats, zinc deficiency is an important factor in esophageal cancer in humans, and it may also be important in human oral cancer. In the present project, oral cancer is to be induced in two groups of rats by 4-nitroquinoline-1-oxide, a proven carcinogen for oral cancer in rats. One group will be fed a zinc-deficient diet (7 ppm) and the other, a zinc-adequate diet (40 ppm). Using a reported successful protocol, the carcinogen will be administered to both groups as a 0.001 percent solution in the drinking water. Rats from both groups will be killed after 16, 22 and 28 weeks exposure to the carcinogen. Comparisons will be made between the two groups with regard to rate of incidence, latency period and gross and microscopic features of cancerous lesions as well as of premalignant signs in clinically normal mucosa.